Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity

Acta Neuropathol. 2010 Jul;120(1):21-32. doi: 10.1007/s00401-010-0649-2. Epub 2010 Feb 7.


Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Astrocytes / ultrastructure
  • Brain / metabolism
  • Brain / pathology
  • Brain / ultrastructure
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • Cytoplasm / ultrastructure
  • Frontotemporal Lobar Degeneration / complications*
  • Frontotemporal Lobar Degeneration / metabolism
  • Frontotemporal Lobar Degeneration / pathology
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Motor Neuron Disease / complications*
  • Motor Neuron Disease / metabolism
  • Motor Neuron Disease / pathology
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Neurofibrillary Tangles / ultrastructure
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neuroglia / ultrastructure
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / ultrastructure
  • Parkinsonian Disorders / complications*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord / ultrastructure
  • Tauopathies / complications*
  • Tauopathies / metabolism
  • Tauopathies / pathology
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • MAPT protein, human
  • tau Proteins